(Adapted from the applicant's abstract) Hematopoietic stem cells (HSC) can be used to treat patients with hematological, genetic, immunological and oncological diseases. To increase the number of patients potentially treated by HSC transplantation, we propose to investigate the use of genetically modified HSC (Gene Therapy) and highly purified HSC (CD34+, CD38- cells). Protocol 1 will evaluate gene therapy for infants with adenosine deaminase (ADA) deficiency and will compare two sources of HSC (cord blood and bone marrow) transduced under a single transduction protocol (daily retroviral supernatant addition in the presence of three growth factors for 72 hours) with an ADA containing retroviral vector. Protocol 2 will evaluate gene therapy for Gaucher disease in adult patients and will compare a single source of HSC (bone marrow) transduced under a single transduction protocol (daily retroviral supernatant addition in the presence of three growth factors for 72 hours) with an ADA containing retroviral vector. Protocol 2 will evaluate gene therapy for Gaucher disease in adult patients and will compare a single source of HSC (bone marrow) transduced under two transduction conditions (six hours incubation with retroviral supernatant without growth factors versus 72 incubation on autologous bone marrow stroma in the presence of retroviral supernatant) with a glucocerebrosidase containing retroviral vector. In both protocols patients will be evaluated for the presence of HSC engraftment in the absence of the administration of marrow ablative therapy. If HSC engraftment is achieved, the patients will be evaluated for expression of the transduced gene. Beside comparing the efficiency of the different transduction protocols, Protocols 1 and 2 will permit a comparison of the capacity of HSC from adults and children to engraft without marrow ablative therapy. Protocol 3 will determine the repopulating capacity of highly purified HSC (CD34+, CD38-cells) in patients who have received myeloid ablative chemotherapy. Patients will be monitored for the rapidity of hematopoietic reconstitution, and the clonality of their post-transplant hematopoiesis determined. Overall this proposal is an attempt to increase the number of patients treated by the transplantation of HSC by using techniques to isolate and/or genetically modify HSC.